Background: Multisystem proteinopathy 1 (MSP1) is an ultrarare disorder caused by a variant in the valosin-containing protein (VCP) gene. MSP1 is inherited in an autosomal dominant pattern and results in progressive disease which may impact various body systems with incomplete penetrance within siblings and across generations. MSP1 often causes progressive myopathy, but can also cause Paget’s disease of bone, frontotemporal dementia, Charcot Marie Tooth, amyotrophic lateral sclerosis, and Parkinsonism. Prospective characterization of the disease using meaningful assessments will not only enable future data driven clinical trial design, but also elevate our understanding of MSP1 to proactively inform clinical care.
Objectives: The purpose of our study was to explore the feasibility and reliability of asynchronous scoring of home-based videos of patients with MSP1, called the VCP Video Assessment (VVA). In addition, we aimed to evaluate the sensitivity of the VVA scorecards in measuring change over 12 months. This study occurred in parallel with an ongoing clinical trial readiness effort which included the North Star Assessment for limb girdle-type dystrophies (NSAD) over the same time period.
Results: A total of 19 patients diagnosed with MSP1 were enrolled in the study and submitted videos across 12 VVA functional tasks, as able, during at least 1 study visit. All patients completed a follow up visit approximately 1 week after their baseline assessment to evaluate test-retest reliability of VVA. Patients were then asked to complete these same videos at 6- and 12-months to evaluate change over time. The most challenging tasks at baseline were ‘Standing Up From Floor’ (mean severity score: 70.8 (SD: 27.0)); Climbs 5 Stairs (mean severity score: 59.0 (SD: 37.1)); Sits Up from Lying (mean severity score: 57.9 (SD: 26.7)); and Raises Hands Above Head (mean severity score: 57.3 (SD: 35.6)). All items demonstrated strong test-retest reliability (ICC: 0.78-0.98, p<0.001). VVA scores were highly and significantly correlated with NSAD at baseline (rho= -0.89, p<0.001) and 12 months (rho= -0.94, p<0.001). All VVA items and the NSAD declined over 12 months, with VVA summed score and NSAD change being significantly correlated (rho= -0.58, p=0.03).
Conclusions: VVA reliably quantified functional ability in patients with MSP1, cross-sectionally and over 12-months with disease progression. VVA may be a useful assessment to consider in future clinical trial planning.